Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.
GROW Research Lab, Narayana Nethralaya Foundation, Bangalore, India.
Asia Pac J Ophthalmol (Phila). 2020 Dec;9(6):533-540. doi: 10.1097/APO.0000000000000332.
Keratoconus (KC) is a corneal ectatic condition characterized by focal structural changes, resulting in progressive thinning, biomechanical weakening, and steeping of the cornea that can lead to worsening visual acuity due to irregular astigmatism and corneal scarring in more advanced cases. It is a relatively common ectatic disease of the cornea predominantly affecting the younger population. Despite its worldwide prevalence, its incidence is rather varied with a higher incidence among the Middle Eastern and South Asian population. Dysregulated corneal extracellular matrix remodeling underlies KC pathogenesis. However, a lack of absolute clarity regarding the factors that initiate and drive progression poses a significant challenge in its prevention and management. KC is a complex multifactorial disease as it is associated with a wide variety of etiological factors such as environmental stimuli/insults, oxidative stress, genetic predisposition, comorbidities, and eye rubbing. A series of studies using corneal tissues (epithelium, stroma), cultured corneal fibroblasts/keratocytes, tear fluid, aqueous humor, and blood from KC subjects has reported significant alterations in various biochemical factors such as extracellular matrix components, cellular homeostasis regulators, inflammatory factors, hormones, metabolic products, and chemical elements. It has become apparent that alterations in the biochemical mediators (related to various etiologies) could contribute to KC pathogenesis by altering the dynamics of extracellular matrix remodeling events such as collagen deposition, degradation, and cross-linking in the cornea. Determining key disease contributing biochemical mediators would aid in disease monitoring, prediction or abatement of disease progression, and development of targeted therapeutics to improve disease prognosis.
圆锥角膜（KC）是一种角膜扩张性疾病，其特征为局灶性结构改变，导致进行性变薄、生物力学减弱和角膜陡峭，在更严重的病例中可导致视力下降，原因是不规则散光和角膜瘢痕。它是一种相对常见的角膜扩张性疾病，主要影响年轻人。尽管其在全球的发病率较高，但发病情况差异较大，在中东和南亚人群中的发病率更高。KC 的发病机制是角膜细胞外基质重塑失调。然而，对于引发和驱动疾病进展的因素缺乏明确认识，这给疾病的预防和管理带来了重大挑战。KC 是一种复杂的多因素疾病，因为它与多种病因有关，如环境刺激/损伤、氧化应激、遗传易感性、合并症和揉眼。一系列使用角膜组织（上皮、基质）、培养的角膜成纤维细胞/角膜细胞、泪液、房水和 KC 患者的血液的研究报告称，各种生化因子如细胞外基质成分、细胞内稳态调节剂、炎症因子、激素、代谢产物和化学元素发生了显著改变。显然，生化介质（与各种病因有关）的改变可能通过改变角膜中细胞外基质重塑事件的动力学，如胶原沉积、降解和交联，从而导致 KC 的发病机制。确定关键的疾病相关生化介质将有助于疾病监测、预测或减缓疾病进展，并开发靶向治疗方法来改善疾病预后。
